Abstract：
:A potent antipsychotic drug candidate, 7-(4-(4-(6-fluorobenzo[d]-isoxazol-3-yl)-piperidin-1-yl)butoxy)-4-methyl-8-chloro -2H-chromen-2-one mesylate(CY611), with good in vitro and in vivo antipsychotic effects was investigated for preformulation evaluation by crystallography methods. Three anhydrous polymorphs(Form I-III), a monohydrate(Form IV), and a NMP solvate(Form V) were discovered and characterized by powder X-ray diffraction, thermal analysis, attenuated total reflection-fourier transform infrared spectroscopy and scanning electron microscopy. Form I, monohydrate Form IV, and a NMP solvate Form V of the drug candidate were isolated, and their structures were determined by single crystal X-ray diffraction. IDR and relative stability experiment were performed. Although Form II has the fastest release rate in water, it easy transformed to monohydrate which has the lowest release rate. In vivo pharmacokinetic study showed that the Form III has the highest bioavailability at 35.4%. Considering the balance between the physicochemical properties, bioavailability and manufacturability of the available polymorphs, Form III may be the optimal form candidate for the eventual formulation.
journal_name
Int J Pharmjournal_title
International journal of pharmaceuticsauthors
Hao C,Chen Y,Xiong J,Yang Z,Gao L,Liu BF,Liu X,Jin J,Zhang Gdoi
10.1016/j.ijpharm.2020.119600subject
Has Abstractpub_date
2020-08-30 00:00:00pages
119600eissn
0378-5173issn
1873-3476pii
S0378-5173(20)30584-6journal_volume
586pub_type
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